Left Atrial Appendage Occlusion An Alternative to Anticoagulation - PowerPoint PPT Presentation

Left Atrial Appendage Occlusion An Alternative to Anticoagulation Jonathon Adams, MD, FACC, FHRS

DISCLOSURE Relevant Financial Relationship(s) None Off Label Usage None Acknowledgement Ken Huber, MD, FACC

OBJECTIVES • Background • What is left atrial appendage occlusion? • How do the efficacy and safety of LAAC compare to OAC? • Who to refer for evaluation?

Atrial Fibrillation → An Epidemic 5 10 Million Million Savelieva, et al. Clin Cardiol 2008;31

Distribution of AF by Age Over 50% of AF occurs in the 6% of the population ≥ 75 years of age WM Feinberg, et al. Arch Int Med 1995;155:469-73

Atrial Fibrillation → Stroke Risk • AF increases the risk of stroke 5-fold (5-6% annual risk) • AF is responsible for 15-20% of all strokes 40% % AF Strokes 30% 20% 10% 0% 50–59 60–69 70–79 80–89 Age (years) • 800,000 strokes/yr in U.S. = 100,000 AF strokes/yr D.R. Holmes . Seminars in Neurology . 2010;30:528 Heart Disease and Stroke Statistical Update: 2009 Circulation , 1-27-09 Stroke 1991;22(18)

Thrombosis/Embolization Electrical Fibrillation Insufficient contraction of LAA Stagnant blood flow Thrombosis / clot formation Thromboembolism Stroke Johnson, EurJ Cardiothoracic Surg 2000;17

LAA – Culprit Location of Thrombi in Left Atrium Left Atrial Appendage Left Atrium 100 90% 80 Frequency (%) in Location 60 LAA 40 20 0 Manning: Circ, '94 Tsai: JFMA, '90 Manning: Circ, '94 Klein: Circ, '94 Total Stoddard: JACC, '95 Aberg: Acta Med Scan, '69 Klein: Int J Card Imag: '93 Leung: JACC, '94 Hart: Stroke, '94 Blackshear et al., Ann Thoracic Surg, 1996;61:755

LAA : Variable Structure

Stroke Prevalence Based Upon Left Atrial Appendage Morphology 20 OR 2.0 14 (0.2-7.2) 12% 12 OR 2.5 15 (1.0-6.1) 10 OR 1.1 Stroke Rate (%) Stroke Rate (%) (0.4-3.2) 8 10 6 OR 0.2 4% 4 (.04-0.8) 5 2 0 0 Chicken Wing Non-Chicken Chicken Windsock Cactus Cauliflower Wing Wing Di Biase, L, et al. JACC 2012

ANTICOAGULATION Hypertrophic Cardiomyopathy Eur Heart J 2012;33:2719-2747

WHAT ABOUT ASPIRIN? AVERROES Study Hazard Apixaban Aspirin Outcome Ratio P Value (N=2808) (N=2791) (95% CI) Stroke or 51 113 0.45 <0.001 systemic embolism (1.6% per yr) (3.7% per yr) (0.32-0.62) 455 Hospitalizationfor 367 0.79 (15.9% per <0.001 cardiovascular cause (12.6% per yr) (0.69-0.91) yr) 44 39 1.13 Major bleeding 0.57 (1.4% per yr) (1.2% per yr) (0.74-1.75) Connolly, et al. NEJM 364;9, 2011

Preventing Stroke in Non-Valvular AF Imputed Benefit of Different Strategies (vs. Control)

Limitations of Anticoagulation Warfarin DOAC • Bleeding risk • Bleeding risk • Daily regimen • Daily or BID regimen • Noncompliance • Noncompliance • INR monitoring • High cost • Drug interactions • Lack of reversal agents • Except Dabigatran

Major Bleeding Treatment Drug D/C Rate Major Bleeding Warfarin 17-28% 3.1-3.6% Dabigatran(150 mg) 21% 3.3% Rivaroxaban(20 mg) 24% 3.6% Apixaban(5 mg) 25% 2.1% Edoxaban (60 mg) 33% 2.8% 1Connolly, S. NEJM 2009; 361:1139-1151 – 2 yrs follow-up (Corrected) 2Patel, M. NEJM 2011; 365:883-891 – 1.9 yrs follow-up, ITT 3Granger, C NEJM 2011; 365:981-992 – 1.8 yrs follow-up, 4Giugliano, R. NEJM 2013; 369(22): 2093-2104 – 2.8 yrs follow-up.

NVAF: Odds of Intracranial Hemorrhage & Age in 145 Case-patients (INR 2.0-3.0) and 870 Controls 5 Intracerebral (> INR) 4 Subdural (> Trauma) Relative Odds 3 2 1 0 < 60 60-64 65-69 70-74 75-79 80-84 ≥85 Age (yrs) MC Fang et al. Ann Int Med 2004;141:745

Significant Undertreatment • Especially those at high risk 40 to 50% not treated 70% 60.7% 58.1% 57.3% 60% Use of Warfarin 50% 44.3% 40% 35.4% 30% 20% % 10% 0% < 55 55-64 65-74 75-84 85+ Age (years) • Levy S, Circulation 1999 • Baker WL , J Man Care Pharm2009 • Samsa, Arch Int Med 2000 • Reynolds MR , Am J Cardiol 2006

Low Warfarin Use in High-risk Patients Warfarin Use • Medicare claims 100% by CHADS 2 Score data, 2006-2007 p<0.001 80% – 27,174 patients 60% 40% – Warfarin use less 20% than 60% 0% 0 1 2 3 4 5 6 CHADS 2 Score • Piccini. Heart Rhythm 2012

Bleeding Risk Assessment ATRIA / HEMORR 2 HAGES / HAS-BLED HAS-BLED Letter Clinical Characteristic Points Awarded H Hypertension 1 Abnormal renal and liver function (1 A 1 or 2 point each) S Stroke 1 B Bleeding 1 L Labile INRs 1 E Elderly (e.g., age > 65 years) 1 D Drugs or Alcohol (1 point each) 1 or 2 Maximum 9 points • Similar predictors for stroke and bleed • Primarily identifies patients at risk for extracranial bleeding Lip GY, JACC 2011 Apostolakis et al. JACC 2013;Dec 12

Net Benefit: Risk / Reward Fundamental Treatment Dilemma • Balance difficult → specific patient CHA 2 DS 2 VAS C % Stroke % Bleed HAS-BLED Low 0 0 0.9 0 Low ? 1 1.3 3.4 1 Mod Mod ? 2 2.2 4.1 2 ? 3 3.2 5.8 3 High High 4 4.0 8.9 4 5 6.7 9.1 5

Atrial Fibrillation – Stroke Non-pharmacologic Treatment

Non-Pharmacologic Options

WATCHMAN LAAC Device • FDA approved alternative to anticoagulation for stroke risk reduction in non-valvular AF • Only device with long-term data from RCTs and multicenter registries • Noninferior to warfarin for stroke risk reduction in nonvalvular AF • Statistically superior to warfarin for hemorrhagic stroke, disabling stroke, and cardiovascular death over long-term follow-up 1. Reddy, V et al. JAMA 2014; Vol. 312, No. 19. 2. Reddy, V et al. Watchman I: First Report of the 5-Year PROTECT-AF and Extended PREVAIL Results. TCT 2014.

WATCHMAN TM Device Minimally Invasive, Local Solution 160 Micron • Available sizes: 21, 24, 27, 30, 33 mm diameter Membrane Intra-LAA design Avoids contact with left atrial wall to help prevent • complications Nitinol Frame Conforms to unique anatomy of the LAA to reduce • embolization risk 10 active fixation anchors - designed to engage • tissue for stability Proximal Face Minimizes surface area facing the left atrium to • reduce post-implant thrombus formation 160 micron membrane PET cap designed to block • emboli and promote healing Anchors Warfarin Cessation 92% after 45 days, >99% after 12 months 1 • 95% implant success rate 1 •

Who is Eligible? The WATCHMAN™ Device is indicated to reduce the risk of thromboembolism from the LAA in patients with non-valvular atrial fibrillation who: • Are at increased risk for stroke and systemic embolism based on CHADS 2 or CHA 2 DS 2 -VASc scores and are recommended for anticoagulation therapy • Are deemed by their physicians to be suitable for short-term warfarin • Have an appropriate rationale to seek a non-pharmacologic alternative to warfarin, taking into account the safety and effectiveness of the device compared to warfarin.

Who is Eligible? • Non-valvular atrial fibrillation • i.e. NOT due to mitral stenosis or prior mitral valve surgery • Stroke risk • CHADS 2 ≥ 2 • CHADS 2 VASc ≥ 3 • Reason to seek non-pharmacologic alternative • Bleeding • Falls • Intolerant of anticoagulation • Compliance issues • Ability to tolerate short-term warfarin (~6 weeks)

Implantation Procedure • One-time implant that does not need to be replaced • Performed in a cardiac cath lab/EP suite, or hybrid OR • Performed by a Watchman Team (EP, IC, Imaging, Anesthesia) • Catheter advanced to the LAA via the femoral vein (Does not require open heart surgery) • General anesthesia* • 1 hour procedure* • 1-2 day hospital stay* * Typical to patient treatment in U.S. clinical trials

WATCHMAN TM Device

Device Endothelialization Canine Model – 30 Day Human Pathology - 9 Months Post-implant Canine Model – 45 Day (Non-device related death)

Post-Implant Management ASA 325 + Warfarin + ASA 325 Clopidogrel ASA 81 TEE Implant 45 Days 6 Months (from implant Indefinite

Warfarin Cessation p = 0.04 Implant success defined as deployment and release of the device into the left atrial appendage Warfarin Cessation PREVAIL Implant Study 45-day 12-month Success No difference between new PROTECT AF 87% >93% and experienced operators CAP 96% >96% Experienced Operators • n=26 PREVAIL 92% >99% • 96% New Operators • n=24 p = 0.28 • 93%

PROTECT AF 5-Year Results Event Rate (per 100 Pt-Yrs) Rate Ratio Posterior Probability WATCHMAN Warfarin (95% CrI) Non-inferiority Superiority 0.61 Primary efficacy 2.2 3.7 >99.9% 95.4% (0.42, 1.07) 0.68 Stroke (all) 1.5 2.2 99.9% 83% (0.42, 1.37) Systemic embolism 0.2 0.0 N/A -- -- Death 0.44 1.0 2.3 >99.9% 98.9% (CV/unexplained) (0.26, 0.90) Source: FDA Oct 2014 Panel Sponsor Presentation.